Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK and NF-kappaB pathway in RAW 264.7 cells

Authors Wang, Ziqiang; Jiang, Wei; Zhang, Zhi; Qian, Min; Du, Bing

Journal JOURNAL OF ETHNOPHARMACOLOGY , OCT 31 2012,1:144

DOI 10.1016/j.jep.2012.08.041 PubMed 22971898

Abstract Ethnopharmacological relevance: Zanthoxylum nitidium (Roxb.) DC. has long been used as a traditional herbal medicine for inflammatory diseases such as rheumatic arthritis and peridentitis. However, the anti-inflammatory mechanism of Nitidine chloride has not been fully elucidated.Aim of the study: To determine the anti-inflammatory effects and mechanism of Nitidine chloride (NTD), a pentacyclic alkaloid is isolated from the root of Z. nitidium, in murine macrophages.Materials and methods: Anti-inflammatory properties of NTD were investigated using lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages as in vitro model. The pro-inflammatory cytokines were evaluated by real-time RT-PCR and ELISA. Furthermore, intracellular signaling pathways were analyzed by Western blot and Immunofluorescence staining using specific antibodies.Results: NTD significantly reduced the production of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 in both RNA and protein level. Moreover, transcriptional activity of NF-kappa B as well as the phosphorylation of mitogen-activated protein kinases (MAPKs) in LPS-treated RAW 264.7 was significantly inhibited by NTD in a dose dependent manner. These results suggested that NTD exerts an anti-inflammatory property by inhibiting TNF-alpha, IL-1 beta, and IL-6 production in association with reduced NF-kappa B and MAPK signaling pathways in RAW 264.7 cells.Conclusion: These results suggested that NTD exerts an anti-inflammatory property by inhibiting TNF-alpha, IL-1 beta, and IL-6 production in association with reduced NF-kappa B and MAPK signaling pathways in RAW 264.7 cells. Nitidine chloride inhibits LPS-induced TNF alpha, IL-1 beta and IL-6 production via the suppression of phosphorylation of MAPK and the translocation of p65. In addition, these results revealed a novel role of NTD in regulation of inflammatory diseases. (C) 2012 Elsevier Ireland Ltd. All rights reserved.